Experiments are directed towards understanding the integrated pathways of regulation and cellular control within immune systems. Recent results suggest that T-cells expressing a regulatory role (helpers and suppressor) and T-cells expressing an effector role (cytotoxic, CTL, or "killer" cells) may be more closely integrated than previously thought. An understanding of the functional relationship and phenotypes of suppressor vs. CTL T-lymphocytes is being approached by the construction of functional and continuously growing cell lines. These are constructed from selected cell populations as they begin to express a phenotypic marker or activity of interest. These cloned T-cell hybridomas and/or T-cell clones derived by other means, are tested for the capacity to simultaneously express different functions. We have obtained a number of clones which bear multiple surface marker phenotypes. While cells of these clones express multiple markers, those that function express only a single function. Several of these clones were derived from T-cell deficient, nude mice and they appear to represent clones of precursor T-cells that are arrested during development. This approach appears promising towards understanding the relationships between regulatory and effector roles of lymphocytes and may foster a better understanding of the total H2 and IR gene control of phenotype within the immune system. The monoclonal cell lines which we develop are also used as experimental targets in order to localize the site of action of microbes and their components in our approach towards understanding immunomodulation by microbial agents. These monoclonal cell targets are facilitating a better understanding of mechanisms by which microbes (bacteria, viruses and protozoa) may inhibit, stimulate or subvert immune systems.